Biochemistry Flashcards
Histone Acetylation
Relaxes DNA coiling allowing transcription
DNA methylation
template strand cytosine and adenine are methylated in DNA replication allowing mismatch repair enzymes to distinguish between old and new strands
Histone methylation
inactivates transcription of DNA
Oratic aciduria
inability to convert orotic acid to UM becase of defect in UMP synthase. Autosommal Recessive
Inceased orotic acid in urine, megaloblastic anemia(doesnt improve with B12 or folate), failure to thrive. No hyperammonemia
Suppplement with oral uridine
Ornithine transcarbamoylase deficiency
Increased orotic acid wit hyperammonemia
Adenosine Deaminase deficiency
Excess ATP and dATP imblances nucleotide pool via feedback inhibition of ribonucleotide reductase preventing DNA synthesis and decreasing lympocyte count ->SCID
Autosommal recessive.
Lesch-Nyhan
Defective purine salvage due to HGPRT deficiency. X linked recessive.
Excess uric acid production which predisposes to gout.
Retardation, self-mutilation, aggression, hyperuriceia, gout, choreoatetosis.
Nucleotide excision repair
Specific endoucleases release the oligonucleotide containing damaged bases; DNA polymerase and ligase fill and reseal the gap
Repairs bulky helix distorting lesions
Xeroderma pigmentosum
prevents repair of pyrimidine dimers because of ultraviolet light exposure
Thiamine-Thiamine
Base excision repair
Specific glycosylases recognize and remove damaged bases, apurinic/apyrimidinic endonuclease cuts DNA at both apurinic and apyrimidinic sites, empty sugar is removed, gap is filled and resealed
Important in repair of spontaneous/toxic deamination
Mismatch repair
newly synthesized strand is recognized, mismatched nucleotide are removed, gap is filled and resealed
Mutated in HNPCC, BRCA1/2
Nonhomologous end joining
Brings together 2 ends of DNA fragments to repair double stranded breaks. No requirement for homology
Mutated in Ataxia telangiectasia
RNA polymerases I, II, III
RNA poly I - rRNA
RNA poly II- mRNA
RNA poly III- tRNA
a-Amantin inhibits RNA polymerase II and can cause hepatotoxicity
Smooth ER functions
Steroid synthesis and detoxification of drugs and poisons.
Liver hepatocytes and steroid hormone cells of the adrenal cortex are rich in SER
I cell disease
Failure of addition of m-6-p to lysosome proteins(enzymes are secreted outside the cell instead of being targeted to the lysosome). Results in coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes. Fatal in childhood
Peroxisome
Catabolism of very long fatty acids and amino acids
Chediak Higashi syndrome
Mutation in lysosomal trafficking regulator gene(LYST), whose product is required for the microtubule dependent sorting of endosomal proetins into late multivesicular endosomes. Results in recurrent pyogenic infections, partial albinism, and peripheral neuropathy
Kartagener’s
Immotile cilia due to dynein arm defect
Infertility, bronchiectasis, recurrent sinusitis, situs inversus.
Vimentin
Connective tissue
Desmin
Muscle
Cytokeratin
epithelial cells
GFAP
Neuroglia
Neurofilaments
neurons
Ouibain inhibitor
Na-K Atpase inhibitor, Binds to K+ site.
Osteogenesis imperfecta
Type 1 collagen defect. Problem forming triple helix during disulfide bond formation.
Brittle bone disease. AD
Multiple fractures with minimal trauma
Blue Sclera
Hearing loss
Dental imperfections(lack of dentin)
Ehlers-danlos
Type 3 collagen defect, problems with covalent cross linkage with Cu2+ lysyl oxidase
Faulty collagen synthesis causing hyperextensible skin, tendency to bleed, hypermobile joints. AD or AR
Associated with joint dislocation, berry aneurysms, organ rupture.
Alport syndrome
Type 4 collage defect
Southern Blot
DNA
Northern Blot
RNA
Southwestern blot
DNA-binding proteins
Codominance
Both alleles contribute to the phenotype of the heterozygote
Variable expressivity
Phenotype varies among individuals with same genotype
NF1
Incomplete penetrance
Not all individuals with a mutant genotype show the mutant phenotype
BRCA1
Pleiotropy
One gene contributes to multiple phenotypic effects
PKU
Imprinting
Differences in gene expression depend on whether the mutation is of maternal or paternal origin
Prader willi and Angelmans syndrome
Anticipation
Increased severity or earlier onset of disease in succeeding generations
Huntingtons
Loss of heterozygosity
If a patient inherits or develops a mutation in a tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops. This is not true of oncogenes
RB- two hit hypothesis
Dominant negative mutation
Exerts a dominant effect. A heterozygote produces a nonfunctional altered protein that also presents the normal gene product from functioning.
linkage disequilibrium
Tendency for certain alleles at 2 linked loci to occur together more often than expected by chance. Measure in a population, not in a family.
Mosaicism
Occurs when cells in the bod differ in genetic makeup due to postfertilization loss or change of genetic information during mitosis.
Locus heterogeneity
Mutations at different loci can produce the same phenotype
Marfans syndrome, albinism
Heteroplasmy
Presence of both normal and mutated mtDNA resulting in variable expression in mitochondrial inherited disease.
Prader WIlli syndrome
Paternal allele is not expressed. Chromosome 15
Mental retardation, hyperphagia, obesity, hypogonadism, hypotonia
Angelman’s syndrome
Maternal allele is not expressed. Chromosome 15
Mental retardation, seizures, ataxia, inappropriate laughter
Mitochondrial myopathies
Group of rare disorders resulting from mutations affecting mitochondrial function. Often presents with myopathy and CNS disease
Ragged Red muscle fibers
Hereditary hemorrhagic telangiectasia (Osler-weber-Rendu syndrome)
Disorder of blood vessels.
Telangiectasia, recurrent epistaxis, skin discolorations, Arterioenous malformatons.
Neurofibromatosis type 1
cafe-au-lait spts, neural tumors, lisch nodules(pigmented iris hamartoas), scolios, optic pathway gliomas
Long arm of chromosome 17
Neurofibromatosis type 2
Bilateral acoustic schwannomas, juvenile cataracts.
Chromosome 22
N-acetylcysteine
Cleaves disulfide bonds within mucous glycoproteins
Duchenne’s Muscular dystrophy
X-linked frameshift mutation. Deletion of dystrophin gene, accelerated muscle breakdown. Weakness begins in pelvic girdle muscles and progresses superiorly. Pseudohypertrophy of calf muscles due to fibrofatty replacement of muscle; cardiac myopathy. Use of Gowers’ maneuver, requiring assitance to stand up.
Onset before 5 years old, increased Creatine kinase due to muscle breakdown
Becker’s muscular dystrophy
X linked mutated dystrophin gene. Less severe than duchennes. Onset in adolescence or early adulthood.
Fragile X syndrome
X linked defect affecting the methylation and expression of the FMR1 gene. Trinucleotide repeat of CGG. The 2nd most common cause of genetic mental retardation after down syndrome.
Extra large testes, ears, jaw
Trinucleotide repeat disease
Fragile X syndrome = CGG
Friedrich’s ataxia = GAA
Huntingtons disease = CAG
Myotonic dystrophy = CTG
Down syndrome clinical findings
Mental retardation, flat facies, prominent epicanthal folds, simian crease, duodenal atresia, congenital heart disease. Increased ALL and alzheimers disease.
decreased a-FP, estriol. Increased B-hCG and inhibin A
Most common cause of genetic mental retardation.
Edwards syndrome
Trisomy 18. Severe mental retardation, rocker bottom feet, micrognathia, low set ears, clenched hands, prominent occiput, congenital heart disease. Death after 1 year of birth`
decreased a-FP, estriol, B-hCG. Normal inhibin A
Patau’s syndrome
sever mental retardation, rocker bottom feet, microphthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, congenital heart disease. Death within 1 year of birth
Trisomy 13.
Decreased B-hCG, PAPP-A and increased nuchal translucency.
Cri-du-chat syndrome
Congenital microdeletion of short arm of chromosome 5.
Microcephaly, moderate to severe mental retardation, high pitched crying/mewing, epicanthal folds, cardiac abnormalities.
22q11 deletion syndromes
CATCH-22 Cleft palate Abnormal facies Thymic aplasia Cardiac defects Hypocalcemia
Kwashiorkor
Protein malnutrition resulting in skin lesions, edema, liver malfunction. Clinical picture is a small child with a swollen belly
MEAL Malnutritrion Edema Anemia Liver(fatty)
Marasmus
Energy malnutrition resulting in tissue and muscle wasting, loss of subcutaneous fat and variable edema.
Pyruvate dehydrogenase complex deficiency
Causes backup of substrate resulting in lactic acidosis. Most cases are due to mutations in X-linked gene for E1-a subunit of PDC
Neurologic defects starting in infancy
Treat with increased intake of ketogenic nutrients Lysine and Leucine.
Superoxide dismutase
O2- to H202
Myeloperoxidase
H202 to HOCL-
NADPH oxidase
O2 to O2-
Essential frutosuria
Involves a defect in fructokinase. Autosomal recessive. A benign, asymptomatic condition since fructose is not trapped in cells. Fructose in blood and urine
Fructose intolerance
Hereditary deficiency of aldolase B. Autosomal recessive. Fructose 1 phosphate accumulates causing a decrease in available phosphate which inhibits glycogenolysis and gluconeogenesis.
Hypoglycemia, jaundice, cirrhosis, vomiting.
Galactokinase deficiency
Hereditary deficiency of galactokinase. Galactitol accumulates if galactose is present in diet. Relatively mild condition. Autosomal recessive.
Galactose in blood and urine, infantile cataracts
Classic galactosemia
Absence of galactose-1-phosphate uridyltransferase. Autosomal recessive. Damage is caused by accumulation of toxic substance(galactitol) in the lens of they eye.
Failure to thrive, jaundice, hepatomegaly, infantile cataracts, mental retardation.
Remove galactose and lactose from diet.
Essential amino acids
PVT TIM HaLL
Phenyalanine
valine
threonine
Tryptophan
isoleucine
methionine
Histidine
a
Leucine
Lysine
Carnitine deficiency
inability to transport LCFAS into the mitochondria, resulting in toxic accumulation causing weakness, hypotonia, and hypoketotic hypoglycemia
Type 1 hyper-chylomicronemia
Increased levels of chylomicrons, TG, cholesterol
AR. Lipoprotein lipase deficiency or altered apolipoprotein C-II. Causes pancreatitis, hepatosplenoegaly, and eruptive/pruritic xanthomas
Type IIa familial hypercholesterolemia
Increased LDL, Choleseterol
AD. Absent or decreased LDL receptors causing accelerated atherosclerosis, tendon xanthomas and corneal arcus
Type IV hypertriglyceridemia
Increased VLDL and TG
AD. Hepatic overproduction of VLDL. Causes pancreatitis.
